Age-related remodeling of apparently normal esophageal epithelia by common cancer drivers
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ABSTRACT:
PROVIDER: EGAC00001001067 | EGA |
REPOSITORIES: EGA
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Project description:Driver mutated clones multi-focally emerged from early adulthood and over years, increase their number and size, ultimately remodeling the entire esophageal epithelia in extreme elderly. Our results suggest that clonal expansion in esophageal epithelia is an inevitable consequence of normal aging, differentially impacting the development of cancer depending on mutation type and exposure to drinking and smoking.
| EGAS00001003008 | EGA
Project description:Prior research establishing that bone interacts in coordination with the bone marrow microenvironment (BMME) to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations. Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells (HSCs) and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling. These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses. A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions. To advance this understanding, herein, we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment. Specifically, we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches. We then discuss unresolved questions and ambiguities that remain in the field.
| S-EPMC10014945 | biostudies-literature
Project description:Acquired, inactivating mutations in Tet methylcytosine dioxygenase 2 (TET2) are detected in peripheral blood cells of a remarkable 5%-10% of adults greater than 65 years of age. They impart a hematopoietic stem cell advantage and resultant clonal hematopoiesis of indeterminate potential (CHIP) with skewed myelomonocytic differentiation. CHIP is associated with an overall increased risk of transformation to a hematological malignancy, especially myeloproliferative and myelodysplastic neoplasms (MPN, MDS) and acute myeloid leukemia (AML), of approximately 0.5% to 1% per year. However, it is becoming increasingly possible to identify individuals at greatest risk, based on CHIP mutational characteristics. CHIP, and particularly TET2-mutant CHIP, is also a novel, significant risk factor for cardiovascular diseases, related in part to hyper-inflammatory, progeny macrophages carrying TET2 mutations. Therefore, somatic TET2 mutations contribute to myeloid expansion and innate immune dysregulation with age and contribute to prevalent diseases in the developed world-cancer and cardiovascular disease. Herein, we describe the impact of detecting TET2 mutations in the clinical setting. We also present the rationale and promise for targeting TET2-mutant and other CHIP clones, and their inflammatory environment, as potential means of lessening risk of myeloid cancer development and dampening CHIP-comorbid inflammatory diseases.
| S-EPMC7014315 | biostudies-literature
Project description:Data-independent acquisition-based proteomics was performed on plasma samples from 60 hospitalized participants, 30 with age-related sarcopenia and 30 without. In the data, label "A" represents "sarcopenia", and "B" represents "non-sarcopenia". This study was approved by the ethics committee of hospital and informed consent were obtained from all participants.
2024-07-07 | PXD053735 |
Project description: Not available
| S-BSST407 | biostudies-other
Project description:PurposeTo establish age-related, normal limits of monocular and binocular spatial vision under photopic and mesopic conditions.MethodsPhotopic and mesopic visual acuity (VA) and contrast thresholds (CTs) were measured with both positive and negative contrast optotypes under binocular and monocular viewing conditions using the Acuity-Plus (AP) test. The experiments were carried out on participants (age range from 10 to 86 years), who met pre-established, normal sight criteria. Mean and ± 2.5σ limits were calculated within each 5-year subgroup. A biologically meaningful model was then fitted to predict mean values and upper and lower threshold limits for VA and CT as a function of age. The best-fit model parameters describe normal aging of spatial vision for each of the 16 experimental conditions investigated.ResultsOut of the 382 participants recruited for this study, 285 participants passed the selection criteria for normal aging. Log transforms were applied to ensure approximate normal distributions. Outliers were also removed for each of the 16 stimulus conditions investigated based on the ±2.5σ limit criterion. VA, CTs and the overall variability were found to be age-invariant up to ~50 years in the photopic condition. A lower, age-invariant limit of ~30 years was more appropriate for the mesopic range with a gradual, but accelerating increase in both mean thresholds and intersubject variability above this age. Binocular thresholds were smaller and much less variable when compared to the thresholds measured in either eye. Results with negative contrast optotypes were significantly better than the corresponding results measured with positive contrast (p < 0.004).ConclusionsThis project has established the expected age limits of spatial vision for monocular and binocular viewing under photopic and high mesopic lighting with both positive and negative contrast optotypes using a single test, which can be implemented either in the clinic or in an occupational setting.
| S-EPMC9805202 | biostudies-literature
Project description:Age is a common risk factor in many diseases, but the molecular basis for this relationship is elusive. In this study we identified 4 disease clusters from 116 diseases in the UK Biobank data, defined by their age-of-onset profiles, and found that diseases with the same onset profile are genetically more similar, suggesting a common etiology. This similarity was not explained by disease categories, co-occurrences or disease cause-effect relationships. Two of the four disease clusters had an increased risk of occurrence from age 20 and 40 years respectively. They both showed an association with known aging-related genes, yet differed in functional enrichment and evolutionary profiles. Moreover, they both had age-related expression and methylation changes. We also tested mutation accumulation and antagonistic pleiotropy theories of aging and found support for both.
| S-EPMC7610725 | biostudies-literature
Project description:Increasing evidence shows that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, particularly in elderly individuals, suggesting that there may still be unidentified causal risk factors. Although the accumulation of somatic DNA mutations is a hallmark of aging, its relevance in cardiovascular disease or other age-related conditions has been, with the exception of cancer, largely unexplored. Here, we review recent clinical and preclinical studies that have identified acquired mutations in hematopoietic stem cells and subsequent clonal hematopoiesis as a new cardiovascular risk factor and a potential major driver of atherosclerosis. Understanding the mechanisms underlying the connection between somatic mutation-driven clonal hematopoiesis and cardiovascular disease will be highly relevant in the context of personalized medicine, as it may provide key information for the design of diagnostic, preventive, or therapeutic strategies tailored to the effects of specific somatic mutations.
| S-EPMC5826570 | biostudies-other
Project description:BackgroundThe association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States.MethodsPatients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables.ResultsOverall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P < 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46-55-year-old patients.ConclusionsFemale EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.
| S-EPMC9314568 | biostudies-literature
Project description:Microbiota plays an essential role in fish growth and health and may be influenced by the changing environmental conditions. Here, we explored the microbiota of wild common sole, one of the most important fishery resources in the Mediterranean Sea, collected from different areas in the North Adriatic Sea. Our results show that the sole microbiota differs from that of the surrounding environment and among the different body sites (gill, skin and gut). Gut microbiota composition showed to be strongly related to fish age, rather than maturity, sex or sampling site. Age-related shifts in gut microbial communities were identified, with increased abundances of Bacteroidia and Desulfobacteria, unveiling potential microbial proxies for age estimation crucial for fisheries management. Our results expand the limited knowledge of the wild common sole microbiota, also in the light of the potential usefulness of the fish microbiota as a tool for future stock identification and connectivity studies.
| S-EPMC11378504 | biostudies-literature